In the first leg, Di Francesco kept faith with the system that helped the Romans stun Barcelona in the quarter-finals at the Stadio Olimpico.
However, an imperious Liverpool side, lead by the divine attacking talents of Mohamed Salah and Roberto Firmino, ran riot, taking full advantage of Roma's three at the back to find the net on no fewer than five occasions.
Cengiz Under was preferred to Patrik Schick in the starting lineup, a move that backfired completely, with the young Turk withdrawn at the break having failed to make an impression.
However, the main talking point following the game was Juan Jesus' struggles up against Salah.
As he has been so often this season, the Egyptian was in fine form, scoring twice and laying on two assists for his team-mates.
Whilst in theory, the decision to deploy three at the back with wing-backs would provide Roma with greater solidity against one of the most fearosme attacking units in world football, it did not play out that way on the pitch.
The 'Reds' caused Roma all sorts of problems, particularly down their left-hand side, with Aleksandar Kolarov consistently being caught overcommitting in attack, leaving Jesus isolated against Salah on the counter.
The Brazilian was no match for Salah's pace and agility, being left for dead on a number of occasions, most notably for Firmino's first goal.
Having already been booked and looking like an accident waiting to happen, Jesus was hooked in the 66th minute and replaced by Diego Perotti as Roma switched to their more familiar four at the back.
That may well be the system we see on Wednesday, with Alessandro Florenzi, Kostas Manolas, Federico Fazio and Kolarov all likely to get the nod.
In theory, this system will limit Liverpool's forward players more as they will not be as readily able to drift into the wide areas and drive forward from deep on the counter as those position will no been manned, however, it is also likely to bring the likes of Tren Alexander-Arnold and Andy Robertson into the game may if they are no longer pegged back by agressive wing-backs.
Both systems have pros and cons, but following Roma's harsh lesson in the first leg they are unlikely to risk the consequences of not changing things this time around.